Posts Tagged ‘chemistry’

A year ago, when chemotherapy stopped working against his leukemia, William Ludwig signed up to be the first patient treated in a bold experiment at the University of Pennsylvania. Mr. Ludwig, then 65, a retired corrections officer from Bridgeton, N.J., felt his life draining away and thought he had nothing to lose.

Doctors removed a billion of his T-cells — a type of white blood cell that fights viruses andtumors — and gave them new genes that would program the cells to attack his cancer. Then the altered cells were dripped back into Mr. Ludwig’s veins.

At first, nothing happened. But after 10 days, hell broke loose in his hospital room. He began shaking with chills. His temperature shot up. Hisblood pressure shot down. He became so ill that doctors moved him into intensive care and warned that he might die. His family gathered at the hospital, fearing the worst.

A few weeks later, the fevers were gone. And so was the leukemia.

There was no trace of it anywhere — no leukemic cells in his blood or bone marrow, no more bulging lymph nodes on his CT scan. His doctors calculated that the treatment had killed off two pounds of cancer cells.

A year later, Mr. Ludwig is still in complete remission. Before, there were days when he could barely get out of bed; now, he plays golf and does yard work.

“I have my life back,” he said.

Mr. Ludwig’s doctors have not claimed that he is cured — it is too soon to tell — nor have they declared victory over leukemia on the basis of this experiment, which involved only three patients. The research, they say, has far to go; the treatment is still experimental, not available outside of studies.

But scientists say the treatment that helped Mr. Ludwig, described recently in The New England Journal of Medicine and Science Translational Medicine, may signify a turning point in the long struggle to develop effective gene therapies against cancer. And not just for leukemia patients: other cancers may also be vulnerable to this novel approach — which employs a disabled form of H.I.V.-1, the virus that causes AIDS, to carry cancer-fighting genes into the patients’ T-cells. In essence, the team is using gene therapy to accomplish something that researchers have hoped to do for decades: train a person’s own immune system to kill cancer cells.

Two other patients have undergone the experimental treatment. One had a partial remission: his disease lessened but did not go away completely. Another had a complete remission. All three had had advanced chronic lymphocytic leukemia and had run out of chemotherapy options. Usually, the only hope for a remission in such cases is a bone-marrow transplant, but these patients were not candidates for it.

Dr. Carl June, who led the research and directs translational medicine in the Abramson Cancer Center at the University of Pennsylvania, said that the results stunned even him and his colleagues, Dr. David L. Porter, Bruce Levine and Michael Kalos. They had hoped to see some benefit but had not dared dream of complete, prolonged remissions. Indeed, when Mr. Ludwig began running fevers, the doctors did not realize at first that it was a sign that his T-cells were engaged in a furious battle with his cancer.

Other experts in the field said the results were a major advance.

“It’s great work,” said Dr. Walter J. Urba of the Providence Cancer Center and Earle A. Chiles Research Institute in Portland, Ore. He called the patients’ recoveries remarkable, exciting and significant. “I feel very positive about this new technology. Conceptually, it’s very, very big.”

Dr. Urba said he thought the approach would ultimately be used against other types of cancer as well as leukemia and lymphoma. But he cautioned, “For patients today, we’re not there yet.” And he added the usual scientific caveat: To be considered valid, the results must be repeated in more patients, and by other research teams.

Dr. June called the techniques “a harvest of the information from the molecular biology revolution over the past two decades.”

Hitting a Genetic Jackpot

To make T-cells search out and destroy cancer, researchers must equip them to do several tasks: recognize the cancer, attack it, multiply, and live on inside the patient. A number of research groups have been trying to do this, but the T-cells they engineered could not accomplish all the tasks. As a result, the cells’ ability to fight tumors has generally been temporary.

The University of Pennsylvania team seems to have hit all the targets at once. Inside the patients, the T-cells modified by the researchers multiplied to 1,000 to 10,000 times the number infused, wiped out the cancer and then gradually diminished, leaving a population of “memory” cells that can quickly proliferate again if needed.

The researchers said they were not sure which parts of their strategy made it work — special cell-culturing techniques, the use of H.I.V.-1 to carry new genes into the T-cells, or the particular pieces of DNA that they selected to reprogram the T-cells.

The concept of doctoring T-cells genetically was first developed in the 1980s by Dr. Zelig Eshhar at the Weizmann Institute of Science in Rehovot, Israel. It involves adding gene sequences from different sources to enable the T-cells to produce what researchers call chimeric antigen receptors, or CARs — protein complexes that transform the cells into, in Dr. June’s words, “serial killers.”

A 94°C geothermal pool, with a level-maintaining siphon, near Gerlach, Nevada. Sediment from the floor of this pool was enriched on pulverized miscanthus at 90°C and subsequently transferred to filter paper in order to isolate microbes able to subsist on cellulose alone.

A record-breaking microbe that thrives while munching plant material at near boiling temperatures has been discovered in a Nevada hot spring, researchers announced in a study published today.

Scientists are eyeing the microbe’s enzyme responsible for breaking down cellulose — called a cellulase — as a potential workhouse in the production of biofuels and other industrial processes.

Cellulose is a chain of linked sugar molecules that makes up the woody fiber of plants. To produce biofuels, enzymes are required to breakdown cellulose into its constituent sugars so that yeasts can then ferment them into the type of alcohol that makes cars (not people) go vroom.

At the industrial scale, this process is done most efficiently at high temperatures that kill other microbes that could otherwise contaminate the reaction, Douglas Clark, a chemical and biomolecular engineer at the University of California at Berkeley, told me today.

“So finding cellulases that can operate at those temperatures are of interest,” he said.

Hot spring
That’s what led Clark, microbiologist Frank Robb from the University of Maryland, and colleagues to collect sediment and water samples from the Great Boiling Springs near Gerlach, Nevada. The spring is 203 degrees F, just short of boiling.

“It’s on private land and has been surrounded by a low wall to keep cattle from going into it and that maintains the temperature,” Robb explained to me today, noting that most hot springs have varying temperatures depending on the weather and water levels in the spring.

In addition, a siphon has been added to Gerlach hot spring to keep it from overflowing. The combination gives whatever microbes that are in there no choice but to grow at high temperatures, Robb noted. Bits of grass and woody material blown into the spring serve as a food source.

The team grew microbes found in the samples on pulverized miscanthus, a type of grass that is a common biofuel feedstock, to isolate the microbes that grow with plant fiber as their only source of carbon.

They then sequenced the community of surviving microbes, which indicated three species of Archaea, a type of single celled microorganism, were able to utilize cellulose as food. Genetic techniques identified the specific cellulase involved in the breakdown of cellulose.

This cellulase, dubbed EBI-244, was found in the most abundant of the three Archaea.

“We didn’t really expect to find an organism that could grow at such a high temperature and degrade cellulose in this particular environment. But you never know,” Clark told me. “It really underscores the diversity of life. And, obviously, if you don’t look, you won’t find it.”

Too hot
The enzyme EBI-244 works optimally at 228 degrees F (109 degrees C), which is actually too hot for the efficient breakdown of cellulose into fermentable sugars due to side reactions that can occur, Clark noted.

“But it is interesting to know that such cellulases are out there,” Clark said. “And then this cellulase might also serve as a good starting point to be engineered to work at a lower temperature but maintain the high stability that it has naturally evolved to work at such high temperatures.”

Robb likened this engineering process to building a street car from parts used on cars found at the racetrack. “The enzyme itself could be the parts bin,” he said.

So, the enzyme itself probably won’t be hard at work anytime soon producing fuel to put in your gas tank, but it does lead researchers down the road to engineering the biofuels of the future. What’s more, EBI-244 is a record holder for heat tolerance in cellulase.

“It is always nice to have a record breaker,” Clark noted. “It adds to that wow factor a little bit.”

A ‘forever young’ drug that allows people to grow old gracefully could be available in just ten years, a leading scientist said last night.

Professor Linda Partridge, an expert in the genetics of ageing, said that the science is moving so quickly that it will soon be possible to prevent many of the ills of old age.

By taking a pill a day from middle-age, we will grow old free from illnesses of the body and mind such as Alzheimer’s and heart disease.

People could work for longer – or simply make the most of their retirement. Some research even suggests skin and hair will retain its youthful lustre.

Professor Partridge, of University College London, said: ‘I would be surprised if there weren’t things within ten years. If told you could take a drug that has minimal side-effects and that’s going to keep you healthy for another five or ten years and then you’ll drop off your perch without disability, most people would want it.’

Extraordinary as the professor’s prediction may seem, it is based on a host of promising scientific studies from around the world.

They have discovered key genes linked to longevity and health – and found ways of tinkering with them, at least in animals.

In one of the remarkable examples, a Harvard University doctor made old mice young again, in experiments that mirrored the plot of The Curious Case Of Benjamin Button, where the lead character played by Brad Pitt ages in reverse.

At the start of the experiment, the animals’ skin, brains, guts and other organs resembled those of an 80-year-old person.

In development: One experiment saw a professor make old mice young again.

Within just two months of being given a drug that switches on a key enzyme, the creatures had grown so many new cells that they had almost completely rejuvenated.

Remarkably, the male mice went from being infertile to fathering large litters.

Other research has shown that chains of reactions in the body involving insulin and related hormones are key to health and ageing. This means that years of research into diabetes could have yielded medicines that can be reinvented as anti-ageing drugs.

Professor Partridge told the Cheltenham Science Festival that some medicines abandoned by drug companies may soon be dusted off and put to use. She said:

‘There are drugs there already, some of them are just sitting in cupboards. I’d be surprised if people don’t start taking them out.

‘The principle is for drugs that if taken from middle-age will ward off quite a broad array of diseases rather than doing things piece-meal or acting when the diseases appear.’

However, she said any drugs would have to be shown to be extremely safe before they were given to healthy people to combat ageing.

Chemistry officials have confirmed the creation of two new elements – so now names will be given to elements 114 and 116.

The periodic table has two new heavyweights, elements 114 and 116, according to a committee of international chemists and physicists.

The elements are fleeting — they are created by bombarding lighter elements together and exist for less than a second before undergoing radioactive decay.

Such a short lifespan means that we can’t say much about them other than they really do exist.

“The lifetimes of these things have to be reasonably long so you can study the chemistry — meaning, pushing a minute,” Paul Karol of Carnegie Mellon University in Pittsburgh, who chaired the committee that approved the new elements, told New Scientist.

The evidence for element’s existence has been mounting for more than a decade. In 1999, for example, Russian scientists with the Joint Institute for Nuclear Research bombarded plutonium-244 with calcium-48 to produce a single atom of 114, which has an atomic weight of 289.

Further collaboration between Russian and U.S. scientists at the Lawrence Livermore National Laboratory resulted in papers published in 2004 and 2006 on the creation of the elements 114, 116, and the yet-to-be-approved 118.

To create 116, the researchers smashed together curium atoms, which have 96 protons in their nucleui, with calcium nuclei, which have 20 protons. This lasted a few milliseconds before decaying into 114, which in turn decayed into copernicum, element 112.

These papers served as the basis for review by the International Union of Pure and Applied Chemistry, which made the formal announcement of the new elements on June 1 with the publication of a paper in Pure Applied Chemistry.

The elements currently go by the placeholder names ununquadium and unuhexium, which by IUPAC convention are derived from the digits 114 and 116.

The Russian discovery team at JINR has proposed flerovium for 114, after Soviet element finder Georgy Flyorov, and muscovium for 116, after Russia’s Moscow region, according to Wired.

The committee also reviewed claims associated with elements 113, 115, and 118, but found they are not yet conclusive and thus do not meet the criteria for discovery.

For more information on how the elements were discovered and the review process, check out the video above from the University of Nottingham’s Periodic Table of Videos series.

By combining high pressure with high temperature, Livermore researchers have created a nanocyrstalline diamond aerogel that could improve the optics for something as big as a telescope or as small as the lenses in eyeglasses.

Aerogels are a class of materials that exhibit the lowest density, thermal conductivity, refractive index and sound velocity of any bulk solid. Aerogels are among the most versatile materials available for technical applications due to their many exceptional properties. This material has chemists, physicists, astronomers, and materials scientists utilizing its properties in myriad applications, from a water purifier for desalinizing seawater to installation on a NASA satellite as a meteorite particle collector.

In new research appearing in the May 9-13 online edition of theProceedings of the National Academy of Sciences, a Livermore team created a diamond aerogel from a standard carbon-based aerogel precursor using a laser-heated diamond anvil cell.

A diamond anvil cell consists of two opposing diamonds with the sample compressed between them. It can compress a small piece of material (tens of micrometers or smaller) to extreme pressures, which can exceed 3 million atmospheres. The device has been used to recreate the pressure existing deep inside planets, creating materials and phases not observed under normal conditions. Since diamonds are transparent, intense laser light also can be focused onto the sample to simultaneously heat it to thousands of degrees.

The new form of diamond has a very low density similar to that of the precursor of around 40 milligrams per cubic centimeter, which is only about 40 times denser than air.

The diamond aerogel could have applications in antireflection coatings, a type of optical coating applied to the surface of lenses and other optical devices to reduce reflection. Less light is lost, improving the efficiency of the system. It can be applied to telescopes, binoculars, eyeglasses or any other device that may require reflection reduction. It also has potential applications in enhanced or modified biocompatibility, chemical doping, thermal conduction and electrical field emission.

In creating diamond aergoels, lead researcher Peter Pauzauskie, a former Lawrence fellow now at the University of Washington, infused the pores of a standard, carbon-based aerogel with neon, preventing the entire aerogel from collapsing on itself.

At that point, the team subjected the aerogel sample to tremendous pressures and temperatures (above 200,000 atmospheres and in excess of 2,240 degrees Fahrenheit), forcing the carbon atoms within to shift their arrangement and create crystalline diamonds.

The success of this work also leads the team to speculate that additional novel forms of diamond may be obtained by exposing appropriate precursors to the right combination of high pressure and temperature.

Researchers say that they’ve found a new class of chemicals that can drive away mosquitoes by disrupting their odor-sensing system — and the first chemical in that class seems to be thousands of times more effective than DEET.

The compound, called VUAA1, was identified thanks to the kind of high-throughput screening process that is more typically used for drug discovery, said Vanderbilt University professor Laurence Zwiebel, a member of the research team. Zwiebel and his colleagues published their findings online this week in the Proceedings of the National Academy of Sciences.

“This compound is really a first-in-class molecule to do this action,” Zwiebel told me today.

A mosquito’s olfactory system relies on a variety of receptors spread out on the bug’s antennae — known odorant receptors, or ORs. The receptors are tuned to respond to different types of odors, including the smell of sweat and blood, and they activate switches called OR co-receptors (Orcos) to tell the mosquito’s brain which scent is being picked up.

Researchers screened almost 120,000 small-molecule compounds to check their effects on human embryonic kidney cells that were genetically engineered to include the OR-Orco complexes. “It was totally a shotgun approach,” Zwiebel said. “Throw the kitchen sink at it and see what happens.”

The scientists were surprised to find that VUAA1 consistently activated the odor-sensing complexes, even though it’s not actually considered an odorant. “It wasn’t something we set out to find. It was an anomaly in our tests,” another member of the Vanderbilt team, graduate student David Rinker, said in a news release.

“If a compound like VUAA1 can activate every mosquito odorant receptor at once, then it could overwhelm the insect’s sense of smell, creating a repellent effect akin to stepping onto an elevator with someone wearing too much perfume, except this would be far worse for the mosquito,” said Patrick Jones, a postdoctoral fellow at Vanderbilt who is the study’s first author.

Zwiebel said that he and his colleagues compared the effectiveness of VUAA1 with that of the widely used DEET insect repellant by measuring how much of each compound it took to repel larval mosquitoes in a petri dish. “The more you use, the more the mosquito moves, as if it’s trying to get out of Dodge,” he explained. A tiny amount of VUAA1 had the same repellent effect as a concentration of DEET that was tens of thousands of times stronger, Zwiebel said.

However, Zwiebel stressed that VUAA1 isn’t yet ready for prime time. “The commercialization of this compound has hardly begun,” he said. The chemical still has to be fine-tuned and checked for toxicity, and it’s possible that other chemicals in the same class will turn out to be more effective or safer. Vanderbilt University says it has filed for a patent on this class of chemicals and is talking with potential corporate licensees about commercialization, with special focus on the development of products to reduce the spread of malaria in the developing world.

Zwiebel noted that VUAA1 has been found to activate the odor-sensing complexes of flies, moths and ants as well. “Basically, every insect that has an olfactory system has this Orco ion channel,” he told me. “We have an expectation that every insect will be affected by this molecule. Now, that’s both good and bad.”

It’s good, because the new class of chemicals may yield new ways to drive away other types of nuisance insects and agricultural pests. But it’d be bad if they also drove away beneficial bugs such as bees and butterflies.

“We’ve all read ‘Silent Spring,’” Zwiebel said. “We don’t want to have the same DDT story.”

Mayo Clinic researchers have designed a new tool for identifying protein function from genetic code. A team led by Stephen Ekker, Ph.D., succeeded in switching individual genes off and on in zebrafish, then observing embryonic and juvenile development. The study appears in the journal Nature Methods.

The work could help shed light on health-related problems such as howcancerous cells spread, what makes some people more prone to heart attacks, or how genes factor in addiction. More complicated issues, like the genetics of behavior, plasticity and cellular memory, stress, learning and epigenetics, could also be studied with this method.

The research at Mayo Clinic’s Zebrafish Core Facility could help further unify biology and genomics by describing the complex interrelations of DNA, gene function and gene-protein expression and migration. The study examines protein expression and function from 350 loci among the zebrafish’s approximately 25,000 protein-encoding genes. Researchers plan to identify another 2,000 loci.

“I consider this particular system a toolbox for answering fundamental scientific questions,” says Dr. Ekker, a Mayo Clinic molecular biologist and lead author of the article. “This opens up the door to a segment of biology that has been impossible or impractical with existing genomics research methods.”

For the First Time

The study includes several technical firsts in genetic research. Those include a highly effective and reversible insertional transposon mutagen. In nearly all loci tested, endogenous expression knockdown topped 99 percent.

The research yielded the first collection of conditional mutant alleles outside the mouse; unlike popular mouse conditional alleles that are switched from “on” to “off,” zebrafish mutants conditionally go from “off” to “on,” offering new insight into localized gene requirements. The transposon system results in fluorescence-tagged mutant chromosomes, opening the door to an array of new genetic screens that are difficult or impossible to conduct using more traditional mutagenesis methods, such as chemical or retroviral insertion.

The project also marks the first in vivo mutant protein trap in a vertebrate. Leveraging the natural transparency of the zebrafish larvae lets researchers document gene function and protein dynamics and trafficking for each protein-trapped locus. The research also ties gene/protein expression to function in a single system, providing a direct link among sequence, expression and function for each genetic locus.

Researchers plan to integrate information from this study into a gene codex that could serve as a reference for information stored on the vertebrate genome.

Shedding Light on Disease

Researchers exposed translucent zebrafish to transposons, “jumping genes” that move around inside the genome of a cell. The transposons instructed zebrafish cells to mark mutated proteins with a fluorescent protein ‘tag.’

“This makes investigation of a whole new set of issues possible,” Dr. Ekker says. “It adds an additional level of complexity to the genome project.”

Dr. Ekker’s team maintains about 50,000 fish in the Zebrafish Core Facility. To observe, photograph and document mutations of that many minnow-sized fish, the team works with an international team of researchers and gets helps from Rochester public elementary school teachers. Under a program with Mayo Clinic and Winona State University called InSciEd Out (Integrated Science Education Outreach), teachers document mutations and learn about the scientific method.